日本研究人员在1月8日出版的《美国人类遗传学会会刊》（The American Journal of Human Genetics，AJHG）上发表论文说，他们发现人体内一处基因变异可使并不肥胖的亚洲人患Ⅱ型糖尿病风险增加。
来自东京大学等机构的研究人员注意到，在包括日本在内的亚洲国家，许多Ⅱ型糖尿病患者并不像欧美国家的Ⅱ型糖尿病患者那样肥胖。为此，他们对日本的糖尿病患者及其家族进行了基因分析，结果发现基因“KCNJ15”上一处碱基的变异与此有关。
研究人员发现，在所有糖尿病患者中，有上述变异的人占10.2%。而在健康人中，存在这种基因变异的只占6.1%。研究人员说，不论胖瘦，基因变异者患Ⅱ型糖尿病的风险为正常人的约1.7倍。而在非肥胖人群中，基因变异者的患病风险则为正常人的约2.5倍。
此外，研究人员还发现，在丹麦，不论是糖尿病患者还是健康人，出现上述基因变异的人所占比例均不到2%。研究人员推测这种变异可能是亚洲人共同的特点。
研究人员指出，这项研究成果揭示了非肥胖型糖尿病的发病机理，将有利于开发相应的治疗方法。而如果有基因变异的人能提前知道自己身体的特点，就能在平时注意生活习惯以预防糖尿病。（生物谷Bioon.com）
生物谷推荐原始出处：
The American Journal of Human Genetics, 8 January 2010 doi:10.1016/j.ajhg.2009.12.009
Identification of KCNJ15 as a Susceptibility Gene in Asian Patients with Type 2 Diabetes Mellitus
Koji Okamoto1, 2, Naoko Iwasaki4, 5, 6, , , Chisa Nishimura1, Kent Doi1, 2, Eisei Noiri2, Shinko Nakamura4, Miho Takizawa4, Makiko Ogata4, Risa Fujimaki4, Niels Grarup8, Charlotta Pisinger9, Knut Borch-Johnsen10, 11, Torsten Lauritzen12, Annelli Sandbaek12, Torben Hansen8, 13, Kazuki Yasuda14, Haruhiko Osawa15, Kishio Nanjo16, Takashi Kadowaki3, Masato Kasuga17, Oluf Pedersen8, 11, 18, Toshiro Fujita2, Naoyuki Kamatani7, Yasuhiko Iwamoto4 and Katsushi Tokunaga1
1 Department of Human Genetics, Graduate School of Tokyo University, Tokyo 113-0033, Japan
2 Department of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
3 Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
4 Diabetes Center, Tokyo Women's Medical University, Tokyo 162-8666, Japan
5 Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo 162-8666, Japan
6 Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo 162-8666, Japan
7 Institute of Rheumatology, Tokyo Women's Medical University, Tokyo 162-8666, Japan
8 Hagedorn Research Institute, 2820 Gentofte, Copenhagen, Denmark
9 Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup, Denmark
10 Steno Diabetes Center, 2820 Gentofte, Copenhagen, Denmark
11 Faculty of Health Sciences, University of Aarhus, 8000 Aarhus, Denmark
12 Department of General Practice, University of Aarhus, 8000 Aarhus, Denmark
13 Faculty of Health Sciences, University of Southern Denmark, 5230 Odense, Denmark
14 Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan
15 Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Ehime 790-8577, Japan
16 First Department of Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
17 Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
18 Institute of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Recent advances in genome research have enabled the identification of new genomic variations that are associated with type 2 diabetes mellitus (T2DM). Via fine mapping of SNPs in a candidate region of chromosome 21q, the current study identifies potassium inwardly-rectifying channel, subfamily J, member 15 (KCNJ15) as a new T2DM susceptibility gene. KCNJ15 is expressed in the β cell of the pancreas, and a synonymous SNP, rs3746876, in exon 4 (C566T) of this gene, with T allele frequency among control subjects of 3.1%, showed a significant association with T2DM affecting lean individuals in three independent Japanese sample sets (p = 2.5 × 10?7, odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.76–3.67) and with unstratified T2DM (p = 6.7 × 10?6, OR = 1.76, 95% CI = 1.37–2.25). The diabetes risk allele frequency was, however, very low among Europeans in whom no association between this variant and T2DM could be shown. Functional analysis in human embryonic kidney 293 cells demonstrated that the risk allele of the synonymous SNP in exon 4 increased KCNJ15 expression via increased mRNA stability, which resulted in the higher expression of protein as compared to that of the nonrisk allele. We also showed that KCNJ15 is expressed in human pancreatic β cells. In conclusion, we demonstrated a significant association between a synonymous variant in KCNJ15 and T2DM in lean Japanese patients with T2DM, suggesting that KCNJ15 is a previously unreported susceptibility gene for T2DM among Asians.
